Special Issue Information

Dear Colleagues,

New generation biomaterials should be able to stimulate specific cellular responses at the molecular level, moving from the concept of inertness to one of bioactivity, e.g. positive interaction at the biomaterial-tissue interface. In many cases the body needs only the temporary presence of a device or implant, in which case fully or partially biodegradable materials are better alternatives than biostable materials. The ideal biodegradable material – polymer, ceramic, metal or composite - should be biocompatible, provide adequate initial mechanical fixation, controllably degradable, and should ultimately be replaced by the regenerated tissue.

A wide range of biodegradable materials is being continuously investigated for biomedical applications, which include traditional and advanced biodegradable polymers, bioceramics and composites as well as a small group of metals and alloys based on magnesium.

Typical applications and research areas of biodegradable polymers include surgery sutures, wound dressing, antibacterial coatings, fixation devices, tissue engineering scaffolds as well as drug and cell delivery platforms. Current research focuses also on the development of biodegradable composites combining synthetic or natural biodegradable polymers and bioactive inorganic fillers, e.g. bioactive glasses and calcium phosphate ceramics, which mimic the structural characteristics of the natural extracellular matrix. Magnesium alloys are promising candidates for several structural biomedical applications due to their degradation ability combined with appropriate mechanical properties as well as good biocompatibility and are being proposed as cardiovascular stents, bone fixation devices and porous bone repair materials.

The present combined special issue in IJMS/Materials will include papers authored by researchers around the world reporting on cutting-edge results in the broad field of biodegradable materials for biomedical applications.

Abstract: In the present work, the crystallization behavior and in vitro–in vivo hydrolysis rates of PLA absorbable reinforcement ligaments used in orthopaedics for the repair and reinforcement of articulation instabilities were studied. Tensile strength tests showed that this reinforcement ligament has similar mechanical properties to Fascia Latta, which is an allograft sourced from the ilio-tibial band of the human body. The PLA reinforcement ligament is a semicrystalline material with a glass transition temperature around 61 °C and a melting point of ~178 °C. Dynamic crystallization revealed that, although the crystallization rates of the material are slow, they are faster than the often-reported PLA crystallization rates. Mass loss and molecular weight reduction measurements showed that in vitro hydrolysis at 50 °C initially takes place at a slow rate, which gets progressively higher after 30–40 days. As found from SEM micrographs, deterioration of the PLA fibers begins during this time. Furthermore, as found from in vivo hydrolysis in the human body, the PLA reinforcement ligament is fully biocompatible and after 6 months of implantation is completely covered with flesh. However, the observed hydrolysis rate from in vivo studies was slow due to high molecular weight and degree of crystallinity.

Abstract: Poly(3-hydroxybutyrate), P(3HB), produced from Bacillus cereus SPV using a simple glucose feeding strategy was used to fabricate P(3HB) microspheres using a solid-in-oil-water (s/o/w) technique. For this study, several parameters such as polymer concentration, surfactant and stirring rates were varied in order to determine their effect on microsphere characteristics. The average size of the microspheres was in the range of 2 µm to 1.54 µm with specific surface areas varying between 9.60 m2/g and 6.05 m2/g. Low stirring speed of 300 rpm produced slightly larger microspheres when compared to the smaller microspheres produced when the stirring velocity was increased to 800 rpm. The surface morphology of the microspheres after solvent evaporation appeared smooth when observed under SEM. Gentamicin was encapsulated within these P(3HB) microspheres and the release kinetics from the microspheres exhibiting the highest encapsulation efficiency, which was 48%, was investigated. The in vitro release of gentamicin was bimodal, an initial burst release was observed followed by a diffusion mediated sustained release. Biodegradable P(3HB) microspheres developed in this research has shown high potential to be used in various biomedical applications.

Abstract: During the last decade, biodegradable metallic stents have been developed and investigated as alternatives for the currently-used permanent cardiovascular stents. Degradable metallic materials could potentially replace corrosion-resistant metals currently used for stent application as it has been shown that the role of stenting is temporary and limited to a period of 6–12 months after implantation during which arterial remodeling and healing occur. Although corrosion is generally considered as a failure in metallurgy, the corrodibility of certain metals can be an advantage for their application as degradable implants. The candidate materials for such application should have mechanical properties ideally close to those of 316L stainless steel which is the gold standard material for stent application in order to provide mechanical support to diseased arteries. Non-toxicity of the metal itself and its degradation products is another requirement as the material is absorbed by blood and cells. Based on the mentioned requirements, iron-based and magnesium-based alloys have been the investigated candidates for biodegradable stents. This article reviews the recent developments in the design and evaluation of metallic materials for biodegradable stents. It also introduces the new metallurgical processes which could be applied for the production of metallic biodegradable stents and their effect on the properties of the produced metals.

Abstract: Structural characterization of poly-L-lactic acid (PLLA) and poly(glycolic acid) (PGA) oligomers containing three units was carried out with an atomistic approach. Oligomer structures were first optimized through quantum chemical calculations, using density functional theory (DFT); rotational barriers concerning dihedral angles along the chain were then investigated. Diffusion coefficients of L-lactic acid and glycolic acid in pure water were estimated through molecular dynamic (MD) simulations. Monomer structures were obtained with quantum chemical computation in implicit water using DFT method; atomic charges were fitted with Restrained Electrostatic Potentials (RESP) formalism, starting from electrostatic potentials calculated with quantum chemistry. MD simulations were carried out in explicit water, in order to take into account solvent presence

Abstract: In this study hydrogels synthesized from agarose and carbomer 974P macromers were selected for their potential application in spinal cord injury (SCI) repair strategies following their ability to carry cells and drugs. Indeed, in drug delivery applications, one of the most important issues to be addressed concerns hydrogel ability to provide a finely controlled delivery of loaded drugs, together with a coherent degradation kinetic. Nevertheless, solute effects on drug delivery system are often neglected in the large body of literature, focusing only on the characterization of unloaded matrices. For this reason, in this work, hydrogels were loaded with a chromophoric salt able to mimic, in terms of steric hindrance, many steroids commonly used in SCI repair, and its effects were investigated both from a structural and a rheological point of view, considering the pH-sensitivity of the material. Additionally, degradation chemistry was assessed by means of infrared bond response (FT-IR) and mass loss.

Abstract: Polyhydroxyalkanoate (PHA) is a biodegradable material with many potential biomedical applications, including medical implants and drug delivery. This study developed a system for screening production strains in order to optimize PHA production in Cupriavidus taiwanensis 184, 185, 186, 187, 204, 208, 209 and Pseudomona oleovorans ATCC 29347. In this study, Sudan black B staining, Infrared (IR) and Gas Chromatography (GC) analysis indicated that the best strain for PHA synthesis is C. taiwanensis 184, which obtains polyhydroxybutyrate (PHB). Cultivation of C. taiwanensis 184 under a pH of 7.0, at 30 °C, and at an agitation rate of 200 rpm, obtained a PHB content of 10% and PHB production of 0.14 g/L. The carbon and nitrogen types selected for analysis of PHB production by C. taiwanensis 184 were gluconic acid and NH4Cl, respectively. Optimal carbon/nitrogen ratio for PHB production was also determined. This study demonstrated a PHB content of 58.81% and a PHB production of 2.44 g/L when thecarbon/nitrogen ratio of 8/1 was selected for C. taiwanensis 184. A two‑stage fermentation strategy significantly enhanced PHB content and PHB production. Under a two-stage fermentation strategy with nutrient‑limited conditions, C. taiwanensis 184 obtained a PHB content of 72% and a PHB concentration of 7 g/L. Finally, experimental results confirmed that optimizing the growth medium and fermentation conditions for cultivating the indigenous C. taiwanensis 184 strain substantially elevated PHB content from 10% to 72% and PHB production from 0.14 g/L to 7 g/L, respectively.

Abstract: Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.